title: Possible site of action of CGRP antagonists in migraine.
abstract: BACKGROUND
  The calcitonin gene-related peptide (CGRP) receptor antagonists olcegepant and telcagepant are very potent drugs. Both are effective in migraine but in doses much higher than would be predicted from receptor binding and other in vitro results. This could perhaps suggest an effect of CGRP antagonists behind the blood-brain barrier (BBB), i.e. in the central nervous system (CNS).
  
  
  METHODS
  Comparison of doses needed for CGRP blocking effect in vitro with dose needed in vivo in man and monkeys. Discussion of these doses in relation to doses needed for anti-migraine activity.
  
  
  RESULTS
  In vivo studies in monkeys and man showed that high doses compared to doses needed in vitro are needed to block capsaicin-induced in skin blood flow, a CGRP-mediated reaction. These doses are close to those needed for anti-migraine activity.
  
  
  CONCLUSIONS
  The apparently high doses of CGRP receptor antagonists, olcegepant and telcagepant needed for anti-migraine effect are not so high after all. They do not allow a conclusion as to whether CGRP antagonists act on peripheral sites or central sites in migraine.
authors.affiliation: University of Copenhagen, Copenhagen, Denmark. ptha@glo.regionh.dk
authors.forename: Peer
authors.initials: P
authors.lastname: Tfelt-Hansen
authors.forename: Jes
authors.initials: J
authors.lastname: Olesen
mesh_terms: D000818:Animals; D001381:Azepines / Q000008:administration & dosage; D001812:Blood-Brain Barrier / Q000187:drug effects*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004151:Dipeptides / Q000008:administration & dosage; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D008881:Migraine Disorders / Q000188:drug therapy*; D010879:Piperazines; D011799:Quinazolines / Q000008:administration & dosage; D013141:Spiro Compounds / Q000008:administration & dosage*
chemical_list: C548781:2-(8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro(4.5)dec-9-yl)-N-(2'-oxo-1,1',2',3-tetrahydrospiro(indene-2,3'-pyrrolo(2,3-b)pyridin)-5-yl)acetamide; D001381:Azepines; D019086:Bridged Bicyclo Compounds, Heterocyclic; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004151:Dipeptides; D007093:Imidazoles; D010879:Piperazines; D011799:Quinazolines; D013141:Spiro Compounds; C525458:telcagepant; C406305:olcegepant